Perinatal brain injury: From pathogenesis to neuroprotection

Brain injury secondary to hypoxic-ischemic disease is the predominant form of ail brain injury encountered in the perinatal period. The focus of this article is the most recent research developments in this field and especial ly those developments that should lead to the most profound effects on inte rventions in the first years of the new millennium. Neuronal injury is the predominant form of cellular injury in the term infant. The principal mecha nisms leading to neuronal death after hypoxia-ischemia/reperfusion are init iated by energy depletion, accumulation of extracellular glutamate, and act ivation of glutamate receptors. The cascade of events that follows involves accumulation of cytosolic calcium and activation of a variety of calcium-m ediated deleterious events. Notably this deleterious cascade, which evolves over many hours, may be interrupted even if interventions are instituted a fter termination of the insult, an important clinical point. Of the potenti al interventions, the leading candidates for application to the human infan t in the relative short-term are mild hypothermia, inhibitors of free radic al production, and free radical scavengers. Promising clinical data are ava ilable for the use of mild hypothermia. (C) 2001 Wiley-Liss, Inc.